12-2236129-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000719.7(CACNA1C):c.477+115699G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,038 control chromosomes in the GnomAD database, including 10,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele (no stars).
Frequency
Genomes: 𝑓 0.35 ( 10258 hom., cov: 32)
Consequence
CACNA1C
NM_000719.7 intron
NM_000719.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.248
Genes affected
CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.477+115699G>A | intron_variant | ENST00000399655.6 | |||
CACNA1C | NM_001167623.2 | c.477+115699G>A | intron_variant | ENST00000399603.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.477+115699G>A | intron_variant | 5 | NM_001167623.2 | ||||
CACNA1C | ENST00000399655.6 | c.477+115699G>A | intron_variant | 1 | NM_000719.7 |
Frequencies
GnomAD3 genomes ? AF: 0.354 AC: 53833AN: 151920Hom.: 10263 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.354 AC: 53869AN: 152038Hom.: 10258 Cov.: 32 AF XY: 0.349 AC XY: 25918AN XY: 74314
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527
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3478
ClinVar
Significance: Uncertain risk allele
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Post-traumatic stress disorder Other:1
Uncertain risk allele, no assertion criteria provided | research | Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry | - | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at